Protoporphyrinogen oxidase is responsible for the seventh step in biosynthesis of protoporphyrin IX. This porphyrin is the precursor to hemoglobin, the oxygen carrier in animals, and chlorophyll, the dye in plants. The enzyme catalyzes the dehydrogenation (removal of hydrogen atoms) of protoporphyrinogen IX (the product of the sixth step in the production of heme) to form protoporphyrin IX. One additional enzyme must modify protoporphyrin IX before it becomes heme. Inhibition of this enzyme is a strategy used in certain herbicides.
UROS: uroporphyrinogen III synthase (congenital erythropoietic porphyria)
Clinical significanceedit
Variegate porphyria is caused by mutations in the PPOX gene. More than 100 mutations that can cause variegate porphyria have been identified in the PPOX gene. One mutation, a substitution of the amino acidtryptophan for arginine at position 59 (also written as Arg59Trp or R59W), is found in about 95 percent of South African families with variegate porphyria. Mutations in the PPOX gene reduce the activity of the enzyme made by the gene, allowing byproducts of heme production to build up in the body. This buildup, in combination with nongenetic factors (such as certain drugs, alcohol and dieting), causes this type of porphyria.
Inhibitors as herbicidesedit
Inhibition of protoporphyrinogen oxidase is a mechanism of action for several commercial herbicides including the nitrophenyl ethers acifluorfen and fomesafen and the pyrimidinediones butafenacil and saflufenacil. The visible symptoms of treatment are chlorosis and desiccation. The damage is caused by an accumulation of protoporphyrin IX in the plant cells by inhibiting protox within the tetrapyrrole biosynthesis pathway.[8] This is a potent photosensitizer which activates oxygen, leading to lipid peroxidation. Both light and oxygen are required for this process to kill the plant.[9][10][11]
^Brzezowski P, Ksas B, Havaux M, Grimm B, Chazaux M, Peltier G, et al. (2019-05-03). "The function of PROTOPORPHYRINOGEN IX OXIDASE in chlorophyll biosynthesis requires oxidised plastoquinone in Chlamydomonas reinhardtii". Communications Biology. 2 (1): 159. doi:10.1038/s42003-019-0395-5. PMC6499784. PMID 31069268.
^Dayan FE, Reddy KN, Duke SO (1999). "Structure-Activity Relationships of Diphenyl Ethers and Other Oxygen-Bridged Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. pp. 141–161. doi:10.1007/978-3-642-58633-0_5. ISBN978-3-642-63674-5.
^Nagano E (1999). "Herbicidal Efficacy of Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. pp. 293–302. doi:10.1007/978-3-642-58633-0_11. ISBN978-3-642-63674-5.
^Dayan FE, Duke SO (2010). "Protoporphyrinogen Oxidase-Inhibiting Herbicides". Hayes' Handbook of Pesticide Toxicology. pp. 1733–1751. doi:10.1016/B978-0-12-374367-1.00081-1. ISBN9780123743671.
Further readingedit
Elder GH (1998). "Genetic defects in the porphyrias: types and significance". Clinics in Dermatology. 16 (2): 225–33. doi:10.1016/S0738-081X(97)00202-2. PMID 9554235.
Maneli MH, Corrigall AV, Klump HH, Davids LM, Kirsch RE, Meissner PN (August 2003). "Kinetic and physical characterisation of recombinant wild-type and mutant human protoporphyrinogen oxidases". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1650 (1–2): 10–21. doi:10.1016/s1570-9639(03)00186-9. PMID 12922165.
Morgan RR, Errington R, Elder GH (January 2004). "Identification of sequences required for the import of human protoporphyrinogen oxidase to mitochondria". The Biochemical Journal. 377 (Pt 2): 281–7. doi:10.1042/BJ20030978. PMC1223874. PMID 14535846.
Sassa S, Kappas A (February 2000). "Molecular aspects of the inherited porphyrias". Journal of Internal Medicine. 247 (2): 169–78. doi:10.1046/j.1365-2796.2000.00618.x. PMID 10692079. S2CID 36820694.
Nishimura K, Taketani S, Inokuchi H (April 1995). "Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli". The Journal of Biological Chemistry. 270 (14): 8076–80. doi:10.1074/jbc.270.14.8076. PMID 7713909.
Dailey TA, Meissner P, Dailey HA (January 1994). "Expression of a cloned protoporphyrinogen oxidase". The Journal of Biological Chemistry. 269 (2): 813–5. doi:10.1016/S0021-9258(17)42182-X. PMID 8288631.
Dailey TA, Dailey HA, Meissner P, Prasad AR (December 1995). "Cloning, sequence, and expression of mouse protoporphyrinogen oxidase". Archives of Biochemistry and Biophysics. 324 (2): 379–84. doi:10.1006/abbi.1995.0051. PMID 8554330.
Meissner PN, Dailey TA, Hift RJ, Ziman M, Corrigall AV, Roberts AG, et al. (May 1996). "A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria". Nature Genetics. 13 (1): 95–7. doi:10.1038/ng0596-95. PMID 8673113. S2CID 11911664.
Dailey TA, Dailey HA (January 1996). "Human protoporphyrinogen oxidase: expression, purification, and characterization of the cloned enzyme". Protein Science. 5 (1): 98–105. doi:10.1002/pro.5560050112. PMC2143237. PMID 8771201.
Puy H, Robréau AM, Rosipal R, Nordmann Y, Deybach JC (September 1996). "Protoporphyrinogen oxidase: complete genomic sequence and polymorphisms in the human gene". Biochemical and Biophysical Research Communications. 226 (1): 226–30. doi:10.1006/bbrc.1996.1337. PMID 8806618.
Deybach JC, Puy H, Robréau AM, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y (March 1996). "Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria". Human Molecular Genetics. 5 (3): 407–10. doi:10.1093/hmg/5.3.407. PMID 8852667.
Lam H, Dragan L, Tsou HC, Merk H, Peacocke M, Goerz G, et al. (January 1997). "Molecular basis of variegate porphyria: a de novo insertion mutation in the protoporphyrinogen oxidase gene". Human Genetics. 99 (1): 126–9. doi:10.1007/s004390050325. PMID 9003509. S2CID 32134586.
Dailey HA, Dailey TA (February 1997). "Characteristics of human protoporphyrinogen oxidase in controls and variegate porphyrias". Cellular and Molecular Biology. 43 (1): 67–73. PMID 9074790.
Frank J, Poh-Fitzpatrick MB, King LE, Christiano AM (August 1998). "The genetic basis of "Scarsdale Gourmet Diet" variegate porphyria: a missense mutation in the protoporphyrinogen oxidase gene". Archives of Dermatological Research. 290 (8): 441–5. doi:10.1007/s004030050333. PMID 9763307. S2CID 32988570.
Roberts AG, Puy H, Dailey TA, Morgan RR, Whatley SD, Dailey HA, et al. (November 1998). "Molecular characterization of homozygous variegate porphyria". Human Molecular Genetics. 7 (12): 1921–5. doi:10.1093/hmg/7.12.1921. PMID 9811936.
Whatley SD, Puy H, Morgan RR, Robreau AM, Roberts AG, Nordmann Y, et al. (October 1999). "Variegate porphyria in Western Europe: identification of PPOX gene mutations in 104 families, extent of allelic heterogeneity, and absence of correlation between phenotype and type of mutation". American Journal of Human Genetics. 65 (4): 984–94. doi:10.1086/302586. PMC1288269. PMID 10486317.
Suzuki Y, Ishihara D, Sasaki M, Nakagawa H, Hata H, Tsunoda T, et al. (March 2000). "Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries". Genomics. 64 (3): 286–97. doi:10.1006/geno.2000.6076. PMID 10756096.
Corrigall AV, Hift RJ, Davids LM, Hancock V, Meissner D, Kirsch RE, Meissner PN (April 2000). "Homozygous variegate porphyria in South Africa: genotypic analysis in two cases". Molecular Genetics and Metabolism. 69 (4): 323–30. doi:10.1006/mgme.2000.2975. PMID 10870850.
Kauppinen R, Timonen K, von und zu Fraunberg M, Laitinen E, Ahola H, Tenhunen R, et al. (April 2001). "Homozygous variegate porphyria: 20 y follow-up and characterization of molecular defect". The Journal of Investigative Dermatology. 116 (4): 610–3. doi:10.1046/j.1523-1747.2001.01293.x. PMID 11286631.
Palmer RA, Elder GH, Barrett DF, Keohane SG (April 2001). "Homozygous variegate porphyria: a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene". The British Journal of Dermatology. 144 (4): 866–9. doi:10.1046/j.1365-2133.2001.04147.x. PMID 11298551. S2CID 41419729.
Corrigall AV, Hift RJ, Davids LM, Hancock V, Meissner D, Kirsch RE, Meissner PN (May 2001). "Identification of the first variegate porphyria mutation in an indigenous black South African and further evidence for heterogeneity in variegate porphyria". Molecular Genetics and Metabolism. 73 (1): 91–6. doi:10.1006/mgme.2001.3163. PMID 11350188.
Donnelly JG, Detombe S, Hindmarsh JT (2002). "Single-strand conformational polymorphism and denaturing gradient gel electrophoresis in screening for variegate porphyria: identification of two new mutations". Annals of Clinical and Laboratory Science. 32 (2): 107–13. PMID 12017191.
External linksedit
PDBe-KB provides an overview of all the structure information available in the PDB for Human Protoporphyrinogen oxidase
protoporphyrinogen, oxidase, protox, enzyme, that, humans, encoded, ppox, gene, ppoxavailable, structurespdbortholog, search, pdbe, rcsblist, codes3nks, 4ivm, 4ivoidentifiersaliasesppox, v290m, protoporphyrinogen, oxidaseexternal, idsomim, 600923, 104968, homo. Protoporphyrinogen oxidase or protox is an enzyme that in humans is encoded by the PPOX gene 5 6 7 PPOXAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes3NKS 4IVM 4IVOIdentifiersAliasesPPOX PPO V290M VP protoporphyrinogen oxidaseExternal IDsOMIM 600923 MGI 104968 HomoloGene 262 GeneCards PPOXGene location Human Chr Chromosome 1 human 1 Band1q23 3Start161 166 056 bp 1 End161 178 013 bp 1 Gene location Mouse Chr Chromosome 1 mouse 2 Band1 1 H3Start171 103 563 bp 2 End171 108 760 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright uterine tubebronchial epithelial cellanterior pituitarycanal of the cervixright lobe of thyroid glandleft lobe of thyroid glandtibial nervebone marrow cellsskin of abdomenspleenTop expressed insacculeyolk sacneural tubeproximal tubulespleenbone marrowbloodliplensbody of femurMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionflavin adenine dinucleotide binding oxidoreductase activity oxygen dependent protoporphyrinogen oxidase activityCellular componentmitochondrial inner membrane mitochondrial intermembrane space intrinsic component of mitochondrial inner membrane membrane mitochondrion integral component of mitochondrial inner membrane mitochondrial membranesBiological processheme biosynthetic process protoporphyrinogen IX metabolic process protoporphyrinogen IX biosynthetic process porphyrin containing compound biosynthetic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez549819044EnsemblENSG00000143224ENSMUSG00000062729UniProtP50336P51175RefSeq mRNA NM 000309NM 001122764NM 001350128NM 001350129NM 001350130NM 001350131NM 001365398NM 001365399NM 001365400NM 001365401NM 008911RefSeq protein NP 000300NP 001116236NP 001337057NP 001337058NP 001337059NP 001337060NP 032937Location UCSC Chr 1 161 17 161 18 MbChr 1 171 1 171 11 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouseprotoporphyrinogen oxidaseHeme synthesis note that some reactions occur in the cytoplasm and some in the mitochondrion yellow IdentifiersEC no 1 3 3 4CAS no 53986 32 6DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteinsProtoporphyrinogen oxidase is responsible for the seventh step in biosynthesis of protoporphyrin IX This porphyrin is the precursor to hemoglobin the oxygen carrier in animals and chlorophyll the dye in plants The enzyme catalyzes the dehydrogenation removal of hydrogen atoms of protoporphyrinogen IX the product of the sixth step in the production of heme to form protoporphyrin IX One additional enzyme must modify protoporphyrin IX before it becomes heme Inhibition of this enzyme is a strategy used in certain herbicides Contents 1 Gene 2 Function 3 Heme biosynthetic pathway 4 Clinical significance 5 Inhibitors as herbicides 6 See also 7 References 8 Further reading 9 External linksGene editThe PPOX gene is located on the long q arm of chromosome 1 at position 22 from base pair 157 949 266 to base pair 157 954 082 Function editThis gene encodes the penultimate enzyme of heme biosynthesis which catalyzes the 6 electron oxidation of protoporphyrinogen IX to form protoporphyrin IX This protein is a flavoprotein associated with the outer surface of the inner mitochondrial membrane 7 Heme biosynthetic pathway editThe following genes encode enzymes that catalyze the various steps in the heme biosynthetic pathway ALAD aminolevulinate delta dehydratase ALAS1 aminolevulinate delta synthase 1 ALAS2 aminolevulinate delta synthase 2 sideroblastic hypochromic anemia CPOX coproporphyrinogen oxidase FECH ferrochelatase protoporphyria HMBS hydroxymethylbilane synthase PPOX protoporphyrinogen oxidase UROD uroporphyrinogen decarboxylase UROS uroporphyrinogen III synthase congenital erythropoietic porphyria Clinical significance editVariegate porphyria is caused by mutations in the PPOX gene More than 100 mutations that can cause variegate porphyria have been identified in the PPOX gene One mutation a substitution of the amino acid tryptophan for arginine at position 59 also written as Arg59Trp or R59W is found in about 95 percent of South African families with variegate porphyria Mutations in the PPOX gene reduce the activity of the enzyme made by the gene allowing byproducts of heme production to build up in the body This buildup in combination with nongenetic factors such as certain drugs alcohol and dieting causes this type of porphyria Inhibitors as herbicides editInhibition of protoporphyrinogen oxidase is a mechanism of action for several commercial herbicides including the nitrophenyl ethers acifluorfen and fomesafen and the pyrimidinediones butafenacil and saflufenacil The visible symptoms of treatment are chlorosis and desiccation The damage is caused by an accumulation of protoporphyrin IX in the plant cells by inhibiting protox within the tetrapyrrole biosynthesis pathway 8 This is a potent photosensitizer which activates oxygen leading to lipid peroxidation Both light and oxygen are required for this process to kill the plant 9 10 11 See also editPorphyrinReferences edit a b c GRCh38 Ensembl release 89 ENSG00000143224 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000062729 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Taketani S Inazawa J Abe T Furukawa T Kohno H Tokunaga R et al October 1995 The human protoporphyrinogen oxidase gene PPOX organization and location to chromosome 1 Genomics 29 3 698 703 doi 10 1006 geno 1995 9949 PMID 8575762 Frank J McGrath JA Poh Fitzpatrick MB Hawk JL Christiano AM July 1999 Mutations in the translation initiation codon of the protoporphyrinogen oxidase gene underlie variegate porphyria Clinical and Experimental Dermatology 24 4 296 301 doi 10 1046 j 1365 2230 1999 00484 x PMID 10457135 S2CID 40509390 a b Entrez Gene PPOX protoporphyrinogen oxidase Brzezowski P Ksas B Havaux M Grimm B Chazaux M Peltier G et al 2019 05 03 The function of PROTOPORPHYRINOGEN IX OXIDASE in chlorophyll biosynthesis requires oxidised plastoquinone in Chlamydomonas reinhardtii Communications Biology 2 1 159 doi 10 1038 s42003 019 0395 5 PMC 6499784 PMID 31069268 Dayan FE Reddy KN Duke SO 1999 Structure Activity Relationships of Diphenyl Ethers and Other Oxygen Bridged Protoporphyrinogen Oxidase Inhibitors Peroxidizing Herbicides pp 141 161 doi 10 1007 978 3 642 58633 0 5 ISBN 978 3 642 63674 5 Nagano E 1999 Herbicidal Efficacy of Protoporphyrinogen Oxidase Inhibitors Peroxidizing Herbicides pp 293 302 doi 10 1007 978 3 642 58633 0 11 ISBN 978 3 642 63674 5 Dayan FE Duke SO 2010 Protoporphyrinogen Oxidase Inhibiting Herbicides Hayes Handbook of Pesticide Toxicology pp 1733 1751 doi 10 1016 B978 0 12 374367 1 00081 1 ISBN 9780123743671 Further reading editElder GH 1998 Genetic defects in the porphyrias types and significance Clinics in Dermatology 16 2 225 33 doi 10 1016 S0738 081X 97 00202 2 PMID 9554235 Maneli MH Corrigall AV Klump HH Davids LM Kirsch RE Meissner PN August 2003 Kinetic and physical characterisation of recombinant wild type and mutant human protoporphyrinogen oxidases Biochimica et Biophysica Acta BBA Proteins and Proteomics 1650 1 2 10 21 doi 10 1016 s1570 9639 03 00186 9 PMID 12922165 Morgan RR Errington R Elder GH January 2004 Identification of sequences required for the import of human protoporphyrinogen oxidase to mitochondria The Biochemical Journal 377 Pt 2 281 7 doi 10 1042 BJ20030978 PMC 1223874 PMID 14535846 Sassa S Kappas A February 2000 Molecular aspects of the inherited porphyrias Journal of Internal Medicine 247 2 169 78 doi 10 1046 j 1365 2796 2000 00618 x PMID 10692079 S2CID 36820694 Nishimura K Taketani S Inokuchi H April 1995 Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli The Journal of Biological Chemistry 270 14 8076 80 doi 10 1074 jbc 270 14 8076 PMID 7713909 Dailey TA Meissner P Dailey HA January 1994 Expression of a cloned protoporphyrinogen oxidase The Journal of Biological Chemistry 269 2 813 5 doi 10 1016 S0021 9258 17 42182 X PMID 8288631 Dailey TA Dailey HA Meissner P Prasad AR December 1995 Cloning sequence and expression of mouse protoporphyrinogen oxidase Archives of Biochemistry and Biophysics 324 2 379 84 doi 10 1006 abbi 1995 0051 PMID 8554330 Meissner PN Dailey TA Hift RJ Ziman M Corrigall AV Roberts AG et al May 1996 A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria Nature Genetics 13 1 95 7 doi 10 1038 ng0596 95 PMID 8673113 S2CID 11911664 Dailey TA Dailey HA January 1996 Human protoporphyrinogen oxidase expression purification and characterization of the cloned enzyme Protein Science 5 1 98 105 doi 10 1002 pro 5560050112 PMC 2143237 PMID 8771201 Puy H Robreau AM Rosipal R Nordmann Y Deybach JC September 1996 Protoporphyrinogen oxidase complete genomic sequence and polymorphisms in the human gene Biochemical and Biophysical Research Communications 226 1 226 30 doi 10 1006 bbrc 1996 1337 PMID 8806618 Deybach JC Puy H Robreau AM Lamoril J Da Silva V Grandchamp B Nordmann Y March 1996 Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria Human Molecular Genetics 5 3 407 10 doi 10 1093 hmg 5 3 407 PMID 8852667 Lam H Dragan L Tsou HC Merk H Peacocke M Goerz G et al January 1997 Molecular basis of variegate porphyria a de novo insertion mutation in the protoporphyrinogen oxidase gene Human Genetics 99 1 126 9 doi 10 1007 s004390050325 PMID 9003509 S2CID 32134586 Dailey HA Dailey TA February 1997 Characteristics of human protoporphyrinogen oxidase in controls and variegate porphyrias Cellular and Molecular Biology 43 1 67 73 PMID 9074790 Frank J Poh Fitzpatrick MB King LE Christiano AM August 1998 The genetic basis of Scarsdale Gourmet Diet variegate porphyria a missense mutation in the protoporphyrinogen oxidase gene Archives of Dermatological Research 290 8 441 5 doi 10 1007 s004030050333 PMID 9763307 S2CID 32988570 Roberts AG Puy H Dailey TA Morgan RR Whatley SD Dailey HA et al November 1998 Molecular characterization of homozygous variegate porphyria Human Molecular Genetics 7 12 1921 5 doi 10 1093 hmg 7 12 1921 PMID 9811936 Whatley SD Puy H Morgan RR Robreau AM Roberts AG Nordmann Y et al October 1999 Variegate porphyria in Western Europe identification of PPOX gene mutations in 104 families extent of allelic heterogeneity and absence of correlation between phenotype and type of mutation American Journal of Human Genetics 65 4 984 94 doi 10 1086 302586 PMC 1288269 PMID 10486317 Suzuki Y Ishihara D Sasaki M Nakagawa H Hata H Tsunoda T et al March 2000 Statistical analysis of the 5 untranslated region of human mRNA using Oligo Capped cDNA libraries Genomics 64 3 286 97 doi 10 1006 geno 2000 6076 PMID 10756096 Corrigall AV Hift RJ Davids LM Hancock V Meissner D Kirsch RE Meissner PN April 2000 Homozygous variegate porphyria in South Africa genotypic analysis in two cases Molecular Genetics and Metabolism 69 4 323 30 doi 10 1006 mgme 2000 2975 PMID 10870850 Kauppinen R Timonen K von und zu Fraunberg M Laitinen E Ahola H Tenhunen R et al April 2001 Homozygous variegate porphyria 20 y follow up and characterization of molecular defect The Journal of Investigative Dermatology 116 4 610 3 doi 10 1046 j 1523 1747 2001 01293 x PMID 11286631 Palmer RA Elder GH Barrett DF Keohane SG April 2001 Homozygous variegate porphyria a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene The British Journal of Dermatology 144 4 866 9 doi 10 1046 j 1365 2133 2001 04147 x PMID 11298551 S2CID 41419729 Corrigall AV Hift RJ Davids LM Hancock V Meissner D Kirsch RE Meissner PN May 2001 Identification of the first variegate porphyria mutation in an indigenous black South African and further evidence for heterogeneity in variegate porphyria Molecular Genetics and Metabolism 73 1 91 6 doi 10 1006 mgme 2001 3163 PMID 11350188 Donnelly JG Detombe S Hindmarsh JT 2002 Single strand conformational polymorphism and denaturing gradient gel electrophoresis in screening for variegate porphyria identification of two new mutations Annals of Clinical and Laboratory Science 32 2 107 13 PMID 12017191 External links editPDBe KB provides an overview of all the structure information available in the PDB for Human Protoporphyrinogen oxidase Portal nbsp Biology Retrieved from https en wikipedia org w index php title Protoporphyrinogen oxidase amp oldid 1189392632 Inhibitors as herbicides, wikipedia, wiki, book, books, library,
